Heat Transfer Baffle System and Uses Thereof

ABSTRACT

This disclosure describes an improved heat transfer system for use in reaction vessels used in chemical and biological processes. In one embodiment, a heat transfer baffle comprising two sub-assemblies adjoined to one another is provided.

RELATED APPLICATIONS

This application claims priority to U.S. Ser. No. 61/240,029 filed Sep.4, 2009.

FIELD OF DISCLOSURE

This disclosure relates to equipment utilized to manufacture chemicalagents, particularly biopharmaceuticals.

BACKGROUND INFORMATION

This disclosure relates to equipment having reaction vessels used tomanufacture chemical and/or biological products such asbiopharmaceuticals. For instance, fermentors commonly provide a reactionvessel for cultivation of microbial organisms or mammalian, insect, orplant cells to produce such products. It is important to control thetemperature of the reaction to ensure optimal production of the product.For example, fermentations typically produce excess heat that must bedissipated or removed from the system to ensure proper reactionconditions. Those of skill in the art have suggested various systems forcontrolling the temperature within reaction vessels, as briefly reviewedbelow. However, there remains a need in the art for improved heatcontrol systems that also incorporates the use of sanitary materialsurfaces, such as that provided herein.

Previously available systems are described in several U.S. and foreignpatents. For instance, U.S. Pat. No. 2,973,944 (Etter, et al.) describesa system of “individual coil units” that each contain a group of tubesthat serve as heat transfer elements in a reaction vessel. The units areindirectly affixed to the inner part of the vessel using bracing memberslocated at the top, bottom, and/or throughout the length of each unit.The '944 patent points out that an advantage of such indirect attachmentis that the expansion and contraction units during will not damage thereactor shell. The units described by the '944 patent are not internal,e.g., part of a baffle, but instead consist of multiple tubes fullyexposed to the reaction vessel. Another tube-based system is describedin U.S. Pat. No. 3,986,934 (Muller, H.) which provides a baffleincluding multiple tubes, the baffle being positioned substantially inthe center of the reaction vessel. The fermentation media is circulatedthrough the baffle such that is contacts the tubes containing the heattransfer media to optimize contact between the reaction components andthe heat transfer media. And U.S. Pat. No. 4,670,397 (Wegner, et al.)discloses a system of tube baffles spaced approximately evenly aroundthe fermentor circumference. The baffles that are positioned apart fromthe fermentor wall, thereby providing a space between the outer shell ofthe fermentor and the baffles.

U.S. Pat. No. 4,985,208 (Sugawara, et al.) illustrates a polymerizationreaction apparatus including multiple heat transfer elements attached tothe inner wall of the reaction vessel between agitating blades. Heattransfer medium may be circulated within an internal passage of the heattransfer elements. The internal passage may be formed in a “zigzag”pattern provided using alternately disposed reinforcing plates.Similarly, U.S. Pat. No. 4,460,278 (Tetsuyuki, et al.) discloses acylindrical vessel with heat exchangers installed between agitatingblades.

Commercially available systems currently offered by manufacturers (e.g.,Tranter, Paul Mueller, Omega) include platecoils, spiral-wound pipesystems, and other vertical pipe loop systems. For instance, thePlatecoil® system provides heat transfer elements constructed from twometal sheets that are resistance welded together to form passagesthrough which heat transfer media is circulated. Platecoils areavailable in various forms and are suitable for insertion within areaction vessel.

The currently available systems do not provide both sufficientstructural integrity for use in high power-per-volume reactors andsanitary construction. The heat transfer systems described hereininclude a baffle described that solves these problems. As describedbelow, the baffle typically has distribution channels through which heattransfer media is circulated and one or more relief channels throughwhich heat transfer media is not circulated, which may also function asa vent for the distribution channels. This construction providesexceptional structural integrity. The baffle is also typically affixedto the reaction vessel such that substantially no seams appear betweenthe baffle and the vessel, thereby providing a surface suitable tosanitization.

SUMMARY OF THE DISCLOSURE

Provided herein are heat transfer systems that efficiently transferheat, withstand the hydraulic forces encountered within a reactionvessel, and may be simply and efficiently sanitized. The heat transferbaffle described herein may be incorporated into heat transfer systemsto solve these problems. In certain embodiments, the baffle has at leastone internal channel and at least two external channels. Typically, heattransfer media is circulated through the distribution channels but notthe one or more relief channels, which may also function as a vent(s)for the distribution channels. The incorporation of distribution andrelief channels into the baffle provides exceptional heat transfercapabilities and the structural integrity necessary to withstand thehydraulic forces encountered in a reaction vessel. Additionally, thebaffle is typically affixed to the reaction vessel such that no seamsappear between it and the vessel, thereby providing a surface suitableto sanitization.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. A. Exemplary embodiment of the reaction vessel equipped withmultiple heat transfer baffles as described herein. B. Exemplarymulti-zone heat transfer baffle.

FIG. 2. Exemplary heat transfer baffle construction.

FIG. 3. Exemplary heat transfer baffle construction.

FIG. 4. Exemplary heat transfer media inlet/outlet cut-outs.

FIG. 5. Exemplary header construction.

FIG. 6. Side-view of exemplary heat transfer baffle.

FIG. 7. Front-view of exemplary heat transfer baffle.

FIG. 8. Results from heat transfer experiment #1.

FIG. 9. Results from heat transfer experiment #2.

DETAILED DESCRIPTION

Described herein are heat transfers systems for use in a reactionvessel. Exemplary reaction vessels may take the form of a chamber,fermentor, bioreactor, or the like, and/or those typically used inchemical reactions, fermentation of microbial organisms, and/or thecultivation of cells (e.g., mammalian, insect or plant-based). A commonproblem associated with the use of such reaction vessels is temperaturecontrol. The reactions are many times extremely exothermic orendothermic, and extreme changes in temperature may affect chemicalreactions, cell growth, and the like. The systems described hereinprovide a robust and novel solution to such problems, such that thetemperature within a reaction vessel may be precisely controlled. Theheat transfer systems described herein efficiently transfer heat,withstand the hydraulic forces encountered within a reaction vessel, andmay be simply and efficiently sanitized.

The heat transfer systems described herein typically include at leastone heat transfer baffle. In certain embodiments, the heat transferbaffle has one or more distribution channels and at least one reliefchannel. Depending upon the embodiment, the baffle may contain a singlerelief channel or multiple relief channels. To indicate this option,this description may refer to the relief channels as relief channel(s)which indicates “one or more relief channels”. The distribution channelsare typically found nearest the exterior of the baffle, and therebycloser to the reaction chamber than the relief channel(s), to providesufficient heat transfer surface area to the reaction chamber interior.The relief channel(s) are typically found between the distributionchannels but may also be alternatively or additionally between orexternal thereto. Heat transfer media is typically circulated throughthe distribution channels but not the relief channel(s). The reliefchannel(s) are typically directly or indirectly vented to the tankexterior through one or more relief holes (e.g., an orifice) to provideboth a means of detecting failure (e.g., leakage) of an distributionchannel and/or preventing the build-up of excess pressure. This ensurescompliance with applicable codes for construction of pressure-containingequipment. This configuration provides a reinforced cross-section,thereby increasing the mechanical strength of the baffle. Venting of therelief channel to the exterior of the reaction chamber may beaccomplished by placing one or more relief holes within such closurebars, for example. The use of such a baffle structure including thedistribution and relief channels into the baffle provides exceptionalheat transfer capabilities and the structural integrity necessary towithstand the hydraulic forces encountered in a reaction vessel (e.g.,in an agitated reaction, high agitator power input per unit volume). Thebaffle may be formed of any suitable material as described herein andconstructed using any available method. For instance, the baffle may beconstructed by assembling various parts (see below) or using a moldingor other technique (e.g., where a moldable material such as plastic isutilized). Described below is a method for assembling the baffle fromits component parts but it should be understood that many other methodsmay be suitable. As such, it is to be understood that a heat transferbaffle having two or more distribution channels for circulation of heattransfer media and at least one relief channel is described herein. Thebaffle may be constructed, made or assembled by any suitable method,using any suitable material as described herein or as may otherwise beavailable to the skilled artisan. Similarly, the baffle may beincorporated into, attached or affixed to a reaction vessel by anysuitable method provided that method provides a substantially seamlessattachment point (e.g., a seamless joint or boundary between materials)to provide a surface that may be simply and efficiently sanitized. A“substantially seamless attachment point”, “seamless joint”, or“crevice-free joint” typically indicates that the boundary between thebaffle and the reaction vessel is substantially undetectable by eithervisual and/or other means (e.g., microscopy). It may also indicate thatthe boundary does not retain any residue from prior reactions followinga standard cleaning procedure typically used by the skilled artisan to“sanitize” such equipment. The system is therefore suitable forsanitization using industry-accepted “clean-in-place” and“sterilize-in-place” systems using any suitable cleaning agent includingbut not limited to detergents, brushes, and/or steam. Such a boundaryaffords itself to simple and efficient sanitization, as defined below.

A surface may be considered sanitized if it is considered “clean” by oneof skill in the art. A surface may be considered sanitized if it is“sanitary” as defined by the American Society of Mechanical Engineers(ASME) with respect to bioprocessing equipment, such as “pertaining toequipment and piping systems that by design, materials of construction,and operation provide for the maintenance of cleanliness so that theproducts produced by these systems will not adversely affect human oranimal health.” A surface may also be considered sanitized when it isfree from microorganisms including but not limited to living ornon-living bacteria and/or viruses, and/or is aseptic as is commonlyunderstood in the art. For chemical reactions, a sanitized surface isone that is substantially free of any detectable chemical residue on thesurface that may be inadvertently incorporated into or otherwiseadversely affect production of the reaction product, the recoverythereof from the vessel, or its use following recovery, for example. Itwould be understood by those of skill in the art that contamination of aproduct to be administered to a human or animal with an organism orcompound not intended to be included in that product could “adverselyaffect” the health of that human or animal. Surfaces containing suchcontaminants are therefore not considered “sanitized” for the purposesof this disclosure.

The distribution channels are typically formed by adjoining at least twomaterials to one another such that one or more channels are formedbetween those materials. It through these channels that heat transfermedia is circulated. The channels may be of any form as long assufficient heat transfer surface area is provided thereby. For instance,the channels may be straight, serpentine, “zig-zag”, etc. A channel mayalso be regular or irregular, as may be found in a dimple jacketmaterial. The distribution channels may also be formed from a singlematerial (e.g., plastic) as described herein. Other embodiments of thedistribution channels as would be known to one of skill in the art arecontemplated herein.

In certain embodiments, the heat transfer baffle may be constructed bymechanically assembling its various parts. For instance, the heattransfer baffle may be assembled by joining two or more heat transfersub-assemblies adjoined to one another in a “back-to-back” configurationand being in communication with flow distribution (“inlet”) andcollection (“outlet”) headers as provided. The heat transfersub-assemblies are typically fabricated from a first material (e.g.,dimple jacket material) adjoined (e.g., welded) to a second material(e.g., a support material). In certain embodiments, the materials areadjoined to form channels for the transport of heat transfer media(e.g., “distribution channels”). For instance, the gaps between thefirst and second materials may form distribution channels through whichheat transfer media may circulate or flow. Two sub-assemblies aretypically affixed to one another. When two sub-assemblies are adjoinedto one another, two distribution channels (e.g., one within eachsub-assembly) and one relief channel (e.g, between the sub-assemblies)are typically formed within a single heat transfer baffle. Thesub-assemblies may be adjoined to one another by any suitable method(e.g., welding, adhesive). Where the material is a form of metal,welding may be particularly useful but other methods may also be useful.For instance, the sub-assemblies may be adjoined using a third materialfashioned into a connecting piece or “closure bar”. This material istypically in communication with each sub-assembly, thereby adjoining thesub-assemblies to one another. The length of this material typicallydetermines the diameter of the relief channel, and accordingly may beadjusted as desired.

The heat transfer baffle may also comprise a first material joined to asecond material such that one or more distribution channels are formed,which may be affixed to another material using a closure bar or thelike. As such, the heat transfer baffle would have the distributionchannel(s) on one side of the baffle, and the relief channel on theother side. The baffle could also be constructed with relief channelsexterior to one or both distribution channels. As such, the baffle couldbe designed to contain, for instance, one, two, three or more reliefchannels that may be between, near or surrounding the distributionchannels. This heat transfer baffle may then be attached to the reactionvessel as described herein (e.g., using attachment arms). Certain ofthese embodiments may be useful where, for instance, more or less heattransfer surface area is required.

The heat transfer baffle is typically attached to the reaction vessel,preferably to the interior wall thereof. As described above, any methodof attachment may be used that provides a substantially seamlessattachment point (e.g., a seamless joint or boundary between materials).The baffle may be attached directly to the reaction vessel, indirectlyusing another piece of material, or both directly and indirectly. Thebaffle may be positioned completely or partially against the interiorwall of the vessel, or the baffle per se may not actually contact theinterior wall of the vessel. For instance, attachment may beaccomplished partially or completely indirectly using a fourth material(e.g., via one or more “attachment arms”). As described above, oneadvantage of the systems described herein is that the system may beefficiently sanitized. Attachment bars or the like may be particularlyuseful for this purpose. For instance, the attachment bars may beadjoined to the sub-assemblies by any suitable method and then adjoinedto the reaction vessel surface using the same or other suitable method.Alternatively, the attachment arms may be adjoined to the reactionvessel surface and then attached to the sub-assemblies. The baffle mayalso be attached to the reaction vessel by, for example, welding thebaffle directly to the reaction vessel. A combination of indirectattachment using, for example, attachment arms, and direct attachment(e.g., by welding the baffle directly to the reaction vessel) may alsobe utilized. Welding is a particularly useful method of attachment asthe attachment bar material provides sufficient material for thedeposition of a strong, ground and/or polished weld bead at the joint.The exterior of the completed assembly is typically mechanicallypolished and/or electro-polished as appropriate to produce a sanitarysurface. In certain embodiments, such as when dimple jacket material isused within the subassemblies, the back-to-back orientation positionsthe usually difficult-to-clean dimple jacket materials on the interiorof the sub-assembly and the support material, which is typically smoothand polished, on the exterior of the sub-assembly. In such anembodiment, the spaces between the dimple jacket material and a supportmaterial form the distribution channels, and the space between thejuxtaposed dimple jacket material forms the relief channel. Such aconfiguration provides a heat transfer system with a sanitary structurethat provides the desired heat transfer capabilities while alsofulfilling the need for a structurally robust mechanical component(e.g., anti-swirl baffle) within a reaction vessel (e.g., during anagitated process).

The heat transfer system also typically includes an inlet and outletheader used to transfer heat transfer media into and out of the baffle.The inlet header is typically in communication with an inlet pipethrough which heat transfer media flows into the distribution channelsof the baffle and the outlet header is typically in communication withan outlet pipe through which heat transfer media flows out of thedistribution channels of the baffle. The relief channel(s) of the baffleare typically not in communication with either the inlet or outletheaders. The inlet and outlet headers distribute and collect heattransfer media flow to and from, respectively, the heat transfersub-assemblies, provide uniform distribution of the heat transfer mediaacross the entire width of the panel, and minimize flow short-circuits,thereby maximizing the effectiveness of the panel surface. In the eventof a leak in the distribution channel, heat transfer media will betypically removed from the system through one or more relief holes whichconnect the relief channel(s) with the tank exterior. In the event of aleak in a distribution channel, the relief channel(s) provide areservoir for the contents of the distribution channel to move, and anexit route from the reaction vessel or those contents (e.g., via therelief hole to the tank exterior). The inlet and outlet headers may befabricated from any suitable material (e.g., pipe) in a tubular or otherappropriate shape, terminating such that the header may be joined to theheat transfer media supply and discharge piping of the system. The inletheader is typically positioned on the baffle below the outlet headerwithin the reaction vessel, but the inlet header may also be positionedon the baffle above the outlet header if desired. Accordingly, where theinlet header is positioned below the outlet header, the heat transferfluid moves from the lower part to the upper part (e.g., bottom-to-top)of the baffle. Where the inlet header is positioned above the outletheader, the heat transfer medium moves from the upper part to the lowerpart (e.g., top-to-bottom) of the baffle. The inlet and outlet headerstypically require one or more slots in the baffle material at thejunction between the header and the exterior chambers of the baffle(e.g., FIG. 4). These slots are positioned such that flow into and outof the baffle is regulated but not adversely affected thereby (e.g.,flow to and from the baffle is not restricted). The headers may comeinto contact with the baffle through the reactor vessel wall (e.g, fromthe side) or from within the reactor vessel, for example. Other suitablearrangements for moving heat transfer media into and out of the bafflesmay also be suitable, as would be understood by the skilled artisan.

The reaction vessel may take any suitable form or shape, but istypically a vertical cylinder (e.g., it may also be horizontal). Thebaffles may protrude at regular or irregular intervals from the innerwall of the reaction vessel. The baffles may also be installed at anysuitable angle relative to the inner wall of the reaction vessel (e.g.,60° relative to the interior wall, 30° relative to the radius, FIG. 3).A suitable angle may be an angle that would be understood by the skilledartisan to be appropriate in order to or sufficient to attenuate theforces (e.g., hydraulic forces) encountered by the baffles resultingfrom motion (e.g., rotational and/or swirl motion) of the vesselcontents resulting from the agitation (e.g., mechanical or otherwise)thereof. A suitable angle is one that would prevent damage to thebaffles from the forces resulting from such motion. Suitable anglesinclude, for example, 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, 45°, 50°,55°, 60°, 65°, 70°, 75°, 80°, 85°, or 90° relative to either theinterior wall of the vessel or the radius of the vessel. Where thereaction vessel contains a mechanism (e.g., mechanical or othermechanism) for agitating or mixing a reaction, such as a set of rotatingblades or the like (e.g., an axial flow or radial flow impeller), thebaffles are affixed to or protrude from the inner wall such that themechanism and the baffles are not in contact with one another. Forinstance, where a device or devices for mixing the reaction componentsis located at the bottom center of the vessel, the baffles may beinstalled above the highest point of said means. Where multiplemechanical mechanisms are utilized, the baffles are typically configuredto avoid those mechanisms. For instance, where the mechanism includesone or more sets of rotating blades, the baffle(s) may be positionedabove, below, between or alongside the blades. The baffle design willensure adequate clearance from the mechanical mechanisms.

The amount of heat transfer surface, and therefore the number and sizeof heat transfer baffles, required will vary depending on the type ofreaction or reaction vessel. The amount required may be calculated bythe skilled artisan using the available methods. As mentioned above, inan agitated reaction, the dimensions of the baffle may be determined atleast in part by the type of mechanism being used for agitation. Inother situations, the dimensions of the baffle may be determined by thesize of the reaction vessel. For instance, in a cylindrical reactionvessel, the depth of the baffle, that is that portion of the baffleextending from the reaction vessel wall toward the interior of thevessel may be estimated to comprise roughly ⅙ to 1/12 (e.g., ⅛, 1/10)the diameter of the reaction chamber. However, it is to be understoodthat other arrangements may also be suitable.

Suitable heat transfer media include and are not limited to fluids andgases. Suitable fluids and gases include and are not limited to steam(top to bottom), hot and cold water, glycol, heat transfer oils,refrigerants, or other pumpable fluid having a desired operationaltemperature range. It is also possible to use multiple types of heattransfer media such that, for instance, one type of media is directed toone area of the reaction vessel and another type of media is directed toa different area of the reaction vessel (e.g., as in the zonal systemdescribed above). Mixtures of heat transfer media (e.g., 30% glycol) mayalso be desirable.

“Fixably attached”, “affixed”, or “adjoined” means that at least twomaterials are bonded to one another in a substantially permanent manner.The various parts described herein may be bonded to one another using,for example, welding, using an adhesive, or another similar process. Theparts must remain attached to one another during use, meaning that thepoints of attachment (e.g., boundaries, joints) between the parts mustbe able to withstand the hydraulic forces encountered within thereaction vessel due to the motion of the reactor contents in response tothe action of the agitator mechanism in addition to the pressurescreated from the heat transfer media flow.

The materials used to produce the equipment described herein may be ofthe same or different composition. The systems described herein aretypically but not necessarily constructed from a corrosion-resistantalloy (e.g., metal). For instance, suitable materials may include,without limitation, dimple jacket material and/or sheet/plate stock.Suitable materials include, for example, carbon steel, stainless steel(e.g., 304, 304L, 316, 316L, 317, 317L, AL6XN), aluminum, Inconel®(e.g., Inconel 625, Chronin 625, Altemp 625, Haynes 625, Nickelvac 625and Nicrofer 6020), Incoloy®, Hastelloy (e.g., A, B, B2, B3, B142T,Hybrid-BC1, C, C4, C22, C22HS, C2000, C263, C276, D, G, G2, G3, G30,G50, H9M, N, 8235, S, W, X), and Monel®, titanium, Carpenter 20®, amongothers. It is understood, however, that other materials besides or inaddition to a corrosion-resistant alloy such as, but without limitation,plastic, rubber, and mixtures of such materials may also be suitable. A“mixture” of materials may refer to either an actual mixture per se toform a combined material or the use of various materials within thesystem (e.g., an alloy reactor shell and rubber baffle components).Regarding the channeled material referred to above, any of the suitablematerials described above may be prepared such that channels are formedthrough which heat transfer media may be distributed.

As mentioned above, one particularly suitable material that may be usedin the baffle is dimple jacket material. Dimple jackets are typicallyinstalled around reaction vessels such as fermentation tanks and may beused as part of a heat transfer system. Dimple jacket material may beused in the devices described herein in the typical fashion, e.g.,wrapped around the reaction vessel. In certain embodiments describedherein, dimple jacket material may be also or alternatively used withinthe baffle structure. Dimple jacket materials are commerciallyavailable, and any of such materials may be suitable for use asdisclosed here. Typically, dimple jacket materials have a substantiallyuniform pattern of dimples (e.g., depressions, indentations) pressed orformed into a parent material (e.g., a sheet of metal). Dimple jacketmaterials may be made mechanically (“mechanical dimple jacket”) or byinflation (e.g., inflated resistance spot welding (RSW)), for example.To prepare a mechanical dimple material, a sheet of metal having asubstantially uniform array of dimples pressed into, where each dimpletypically contains a center hole, is welded to the parent metal throughthe center hole. An inflated RSW dimple material is typically made byresistance spot welding an array of spots on a thin sheet of metal to amore substantial (e.g., thicker) base material (e.g., metal). The edgesof the combined material are sealed by welding and the interior isinflated under high pressure until the thin material forms a pattern ofdimples. Mechanical dimple materials, when used as jackets, typicallyhave high pressure ratings and low to moderate pressure drop, while RSWdimple jackets typically exhibit moderate pressure ratings and a high tomoderate pressure drop. Other suitable dimple materials are available tothose of skill in the art and would be suitable for use as describedherein.

The reaction vessel may take the form of a reaction chamber, fermentor,bioreactor, or the like. The vessel is suitable for chemical reactions,fermentation of microbial organisms, cultivation of cells (e.g.,mammalian, insect or plant-based), or other uses. The reaction vesseland associated heat transfer system may therefore be used in a methodfor controlling the temperature of a chemical, pharmaceutical orbiological process in a vessel comprising an internal reaction chambercomprising at least one of the heat transfer assembly described herein.The process includes distributing a heat transfer medium through theheat transfer distribution channel of the at least one heat transferassembly such that heat resulting from or required by the process istransferred from or to the reaction vessel by the heat transfer medium,thereby removing or adding heat from or to the reaction vessel. Othersuitable applications of the systems described herein would be known toone of skill in the art.

Methods for controlling the temperature of a process in a reactionvessel by circulating heat transfer medium through the distributionchannel of the at least one heat transfer baffle described herein arealso provided. The methods may be used in, for example, a chemicalprocess, a pharmaceutical process, a biological process, or otherprocess. Biological processes may be, for example, a microbiologicalculture, mammalian cell culture, plant cell culture, or the like. Themethod may also be used in at least one step in the production of avaccine. The method is typically be carried out by pumping a heattransfer fluid into the heat transfer baffle through, for example, theinlet header which is in communication with a source or reservoir ofheat transfer fluid. The temperature of the heat transfer fluid istypically higher or lower than the temperature of the contents ofvessel, depending on whether the temperature of the contents of thevessel are to be increased or decreased, respectively. The temperatureof the heat transfer fluid may be adjusted as necessary in order toachieve the desired temperature of the vessel contents. The fluid istypically circulated through the heat transfer baffle and exits through,for example, the outlet header for further processing (e.g., heating orcooling) and/or re-circulation through the baffle. The temperature ofthe vessel contents is thereby altered to or maintained as desired bythe user. Other suitable methods for using the systems described hereinwould be known to one of skill in the art.

An exemplary embodiment of the heat transfer system is shown in FIG. 1A.As shown therein, heat transfer baffle 2 is affixed to the interior 1 ofreaction vessel 6 using attachment arms 7 (which may or may not extendto the entire width of the baffle). In the particular embodiment shownin FIG. 1A, the baffle is indirectly attached to the reaction vessel anddoes not directly contact the vessel. The baffle is typically incommunication with inlet header 3 through which heat transfer fluidenters the baffle and an outlet header 4 through which heat transfermedium exits the baffle. In this embodiment, the baffles are attached tothe reaction vessel above, below, or alongside a mechanism for mixing(5) the vessel contents. The mechanism for mixing the reactioncomponents may be, e.g., an impeller system that may extend any lengthalong the vessel as indicated by the dashed lines. Suitable impellarsystems include but are not limited to, e.g., any manner and/or singleand/or multiple and/or combination of axial flow and radial flow openimpellers. The baffles are typically adjoined to the interior of thereaction vessel shell through attachment arms 7 by a welding or otherprocess that results in a substantially seamless joint between thebaffle and the reaction vessel. Thus, as typically constructed, thereaction vessel shell and the baffle may appear to form a single unit.This provides significant advantages in that the heat transfer systemmay be efficiently cleaned and/or sanitized, preferably leaving noresidue at the joint.

The baffles may also be constructed such that heat transfer media iscirculated within one or more compartments or zones of the baffle andtherefore the reaction vessel. For instance, as shown in FIG. 1B, thebaffles may be separated from one another by partition 8 to formindependent intra-baffle compartments such that heat transfer media maybe circulated through each compartment. The heat transfer media may becirculated through each compartment either in series or independentlyfrom any other compartment. Independent circulation typically requireseach compartment or zone to comprise an inlet and outlet header attachedfor each compartment. The inlet and outlet headers may be incommunication with one another or independent from one another. A valveor other mechanism for selecting particular baffles and/or inlet and/oroutlet headers may also be provided. In this manner, heat transfer mediamay be circulated within particular areas (e.g., substantially the top,bottom, or middle) of the reaction vessel. This is useful where, forinstance, the volume of the reaction is increased or decreased overtime, such that more of less heat transfer surface area is required. Thebaffle may also be installed horizontally with respect to the reactionchamber, meaning that instead of running the top and bottom length ofthe chamber, the baffle would run across the chamber from side-to-side.Other suitable baffle orientations are contemplated herein as would beunderstood by one of skill in the art.

FIGS. 2, 3, and 5-7 illustrate exemplary baffles or portions thereof. Asdiscussed above, the baffle is typically joined to inlet header 3 andoutlet header 4. These headers are adjoined to the baffle such that theheat transfer media circulates through distribution channels 9. Reliefchannel(s) 10 are typically vented to the exterior of the vessel using,for instance, a relief hole (which may be found within a closure bar,for example). The inlet and outlet headers are not in communication withrelief channel(s) 10, through which heat transfer media does nottypically circulate due to design requirements regarding pressurecontaining equipment. Thus, the distribution and relief channels do notcommunicate, unless a leak forms within a distribution channel such thatheat transfer medium or other material moves into the relief channel(s)and is vented from the baffle and reaction vessel. Distribution channels9 are typically formed between the support material 11 and dimple jacketmaterial 12 of each sub-assembly. Relief channel(s) 10 are typicallyformed by adjoining two sub-assemblies, each comprising support material11 fixably attached to dimple jacket material 12 to one another. In suchembodiments, the dimple jacket material and support material of eachsub-assembly are typically adjoined to one another by welding or otherprocess resulting in the materials being fixably attached to oneanother. The sub-assemblies are typically adjoined to one another usingclosure bars 13. The closure bar is typically adjoined to the supportmaterial by a welding or other process that results in a substantiallyseamless joint. The width of the closure bar may be adjusted to set thewidth of the relief channel as desired (e.g., setting the juxtaposeddimple jacket material closer together or further apart). One or morerelief holes may be made within the closure bars such that reliefchannel(s) may communicate with the reaction vessel exterior. The baffleassembly is typically fixably attached to the vessel through attachmentarm or arms 7 by a welding or other process that results in asubstantially seamless joint. As described above, use of the attachmentarms advantageously provides for efficient cleaning and/or sanitizationof the baffles in that very little to no residue remains at the jointbetween the interior surface of the reaction vessel and the bafflefollowing the attachment process (e.g., welding).

A better understanding of the present invention and of its manyadvantages will be had from the following examples, given by way ofillustration.

EXAMPLES Example 1 Baffle Construction

Construction of a heat transfer baffle as described herein wasaccomplished using essentially the steps described below:

-   1. The baffle material was cut to size. Heat transfer media    inlet/outlet slots were cut in both ends of baffle material.-   2. The baffle material was affixed into adequate jigs and fixtures    to protect the baffle material from warping from heat build-up    during the welding process. Warping can cause the baffle material to    lose its desired shape.-   3. Dimples were punched into the heat transfer material to create    attachment points to weld heat transfer material onto baffle    material. Punching the dimples in the heat transfer material creates    an open ‘pillow’ section between the dimple spots. The creation of    this ‘pillow’ section allows heat transfer media to flow properly    throughout the heat transfer surface. The heat transfer material was    cut to size and the edges crimped to allow the perimeter of the    dimpled heat transfer surface to be welded to the baffle material.-   4. The dimpled heat transfer material was welded onto baffle    material. The welding sequence of the dimples and the perimeter    edges was properly spaced in order to decrease the amount of heat    build-up in the two materials being welded. Too much heat in any    area at one time can cause the materials to warp, causing the baffle    to lose its desired shape.    Note: In order to create one sanitary heat transfer baffle assembly,    it is typically necessary to fabricate two sub-assemblies of    baffle/heat transfer material as described in steps #1 through #4    above.-   5. The baffle closure bars were cut to length.-   6. Two baffle/heat transfer sub-assemblies were positioned with    their heat transfer surfaces facing each other. The baffle material    was aligned such that the surfaces were parallel with each other and    the edges aligned.-   7. The baffle closure bars were used to create the adequate spacing    between the baffle/heat transfer sub-assemblies (e.g., thereby    providing the relief channel(s)), and the weld closure bars were    tacked in place. Final spacing, position and “squareness” of the    baffle assembly was checked before final welding.-   8. The baffle assembly was affixed into adequate jigs and fixtures    to protect baffle assembly from warping from heat build-up during    the welding process. Warping can cause the baffle assembly to lose    its desired shape.-   9. The baffle closure bars were then welded into position. The    welding sequence of the baffle closure bars was spaced in order to    decrease the amount of heat build-up in the materials being welded.    Too much heat in any area at one time can cause the materials to    warp, causing the baffle assembly to lose its desired shape.-   10. The inlet/outlet header pipes were cut to length and header    pipes notched along the middle of one side to accept baffle    assembly.-   11. The inlet/outlet header caps were notched along the middle to    accept baffle assembly.-   12. The baffle supports were cut to length and notches cut along the    middle of one end to accept baffle assembly.-   13. The inlet/outlet header pipes were welded into place.-   14. The inlet/outlet header caps were welded into place.-   15. The baffle supports were welded into place.-   16. All welds were ground smooth and flush ensuring that no crevices    are allowed. All surfaces are to be smooth with no crevices in order    to achieve a sanitary finish.-   17. The baffle assembly exterior surfaces are to be completely    electro-polished if a smoother surface finish is required.

Example 2 Heat Transfer Testing

The heat transfer system was constructed essentially as described inExample 1 and tested using the following parameters:

-   -   1. Six (6) heat transfer baffles were installed in a vertical        cylindrical vessel in the manner illustrated in FIG. 1A.        -   i. Each baffle was 12″ (305 mm) wide×168″ (4,267 mm) long.        -   ii. Baffles were installed at an angle of 30° relative to            the vessel radius.        -   iii. Baffles were oriented into the flow exiting the            agitator impellers.        -   iv. The vessel was 72″ (1,829 mm) diameter×195″ (4,953 mm)            with ASME dished heads.            -   1. Vessel total volume: 14,000 liters            -   2. Vessel working volume: 10,000 liters    -   2. The vessel was equipped with a 100 hp (75 kW) agitator        -   i. Agitator maximum speed: 159 rpm (2.65 s⁻¹)        -   ii. Impeller configuration: four (4) on vertical centerline            -   1. Lower, lower-middle: Rushton turbines, 32.5″ (826 mm)                diameter            -   2. Upper-middle, upper: High-solidity hydrofoils, 34″                (864 mm) diameter    -   3. Instrumentation was installed and available to make the        following measurements:        -   i. Temperature: Thermocouples were installed in thermowells            to measure the temperature of the vessel contents (two            probes) and baffle coolant supply and discharge temperature.            Temperature data points were collected and stored using a            Kaye Validator data logger.        -   ii. Baffle coolant flow velocity was measured using an            ultrasonic flowmeter with its transducer positioned on the            coolant supply piping.        -   iii. Agitator operating speed was set using the fermenter            automation control system            -   1. The automation system agitator speed control was                calibrated during set-up using a hand-held optical                tachometer.            -   2. Agitator speed was verified during the tests using                the same calibrated optical tachometer.        -   iv. Agitator wire power draw was measured using a digital            power meter to monitor all three legs of the power to the            motor's AC variable frequency drive.        -   v. The mass of the vessel contents was determined using            calibrated differential pressure transducers.    -   4. The vessel was charged with 10,000 liters (kilograms) of        de-ionized water at ambient conditions and the temperature of        the contents was raised to 70° C. by direct steam injection. The        final mass of the contents was recorded after steam injection to        account for the addition of the resulting steam condensate.    -   5. The agitator speed was set at a value to deliver        approximately 80% of full motor power for the first test;        subsequent tests were conducted at speeds selected to yield        power levels at approximately 50% and 25% of the initial value.    -   6. Coolant (chilled water) was re-circulated through the baffle        assembly using a skid-mounted chiller and pump.        -   i. Coolant flow was adjusted to the desired rate using a            valve to throttle the discharge flow of the circulating            pump.        -   ii. Coolant velocity was measured using an ultrasonic            flowmeter as noted above; volumetric flow rate was            calculated as the product of velocity and pipe            cross-sectional area.        -   iii. Tests were conducted over a range of coolant flow rate.        -   iv. The reported total coolant flow is equally divided among            the six baffles by hydraulic balancing which is inherent in            the design of the baffle coolant supply and discharge piping            and headers.    -   7. Vessel batch temperature as well as coolant supply and        discharge temperature were logged simultaneously at a rate of        once per minute as the batch was cooled from 70° C. to 25° C.        for a given set of coolant flow and agitator operating speed        (FIG. 8).    -   8. The heat transfer rate Q over the course of the test is        calculated from the data based on the mass of the batch and the        minute-by-minute change in batch temperature using the        relationship

Q=m·c _(P) ·ΔT·60

-   -   where Q=heat transfer rate, BTU/hr        -   m=mass of vessel contents, lb_(m)            -   c_(p)=heat capacity of vessel contents, BTU/lb_(m)-° F.            -   ΔT=temperature change per minute (e.g. T_(t+1)−T_(t)), °                F.

The overall heat transfer coefficient U is then calculated over thecourse of the test per the relationship

Q=U·A·ΔT _(ln)

-   -   where Q=heat transfer rate, BTU/hr        -   U=overall heat transfer coefficient, BTU/hr-ft²-° F.            -   A=available area for heat transfer, ft²            -   ΔT_(ln)=log mean temperature driving force, ° F.

The above approach was used because the coolant inlet temperature didnot stay constant but rather changed (decreased) over the course of thetest and cycled with the operation of the chiller; coolant temperaturewas in the range of 54° C. to 12° C. for all tests. The resulting valueof U likewise decreases over the course of the test and all comparisonsare made at the batch temperature of interest, in this case, 37° C.

-   -   -   Note that the above approach which is based on the change in            batch temperature is conservative since a heat balance based            on the change (increase) in coolant temperature yielded a            higher heat load.

As shown in FIG. 9, the heat transfer system is capable of efficientlytransferring heat from a reaction mixture. In the operating range ofinterest (37° C.), the tests yielded a U value in excess of 200BTU/hr-ft²-° F.; this compares very favorably to cooling-service valuesthat are claimed for both external jackets (100-130) and internalstructures (conventional helical coils and vertical tube bundles: 100;platecoils: 90-160). Even at low flow rates on the order of 100 gpm forsix baffles (˜17 gpm each) the measured heat transfer coefficient isgreater than or equal to that for other devices.

Data collected at the maximum coolant flow rate tested and agitatorpower input levels associated with the operation of microbial fermenters(8-29 hp/kgal or 1.6-5.7 kW/m³) indicated that overall heat transfercoefficient U was relatively constant (237±6 BTU/hr-ft²-° F.) over therange examined.

All documents cited or referred to herein are hereby incorporated byreference in their entirety into this description. While the descriptionprovided herein may be presented in terms of the preferred embodiments,it is understood that variations and modifications will occur to thoseskilled in the art. Therefore, it is intended that the appended claimscover all such equivalent variations that come within the scope of theclaimed subject matter.

1-16. (canceled)
 17. A method for controlling the temperature of a process in a reaction vessel, the process comprising circulating heat transfer medium through at least one heat transfer baffle comprising: a. first sub-assembly consisting essentially of a first material adjoined to a second material to form a first distribution channel, b. a second sub-assembly consisting essentially of a first material adjoined to a second material to form a second distribution channel, c. a closure bar that adjoins the first assembly and the second sub-assembly to one another; and d. a relief channel between the first sub-assembly and the second sub-assembly; wherein: the closure bar sets the width of the relief channel, and the distribution channels and the relief channel do not communicate unless a leak forms within a distribution channel.
 18. The method of claim 17 wherein the heat transfer medium is selected from the group consisting of steam, a pumpable fluid, water, glycol, a heat transfer oil, a refrigerant, and combinations thereof.
 19. The method of claim 18 wherein the heat transfer medium is water.
 20. The method of claim 17 wherein the process is selected from the group consisting of a chemical process, a pharmaceutical process, and a biological process.
 21. The method of claim 20 wherein the biological process is selected from the group consisting of microbiological culture, mammalian cell culture, and plant cell culture.
 22. The method of claim 20 wherein the process is at least one step in the production of a vaccine.
 23. (canceled)
 24. The method of claim 17 wherein the heat transfer baffle comprises two or more distinct compartments through which heat transfer media may be circulated independently of any other compartment.
 25. The method of claim 17 wherein the at least one heat transfer baffle is adjoined to the reactor vessel.
 26. The method of claim 25 wherein the one or more heat transfer baffles are adjoined to the reactor vessel through a substantially seamless joint boundary between the baffle and the vessel.
 27. The method of claim 17 wherein at least one distribution channel is adjoined to a heat transfer media inlet header.
 28. The method of claim 17 wherein at least one distribution channel is adjoined to a heat transfer media outlet header.
 29. The method of claim 17 wherein at least one distribution channel is adjoined to a heat transfer media inlet header and a heat transfer media outlet header.
 30. The method of claim 17 wherein the at least one heat transfer baffle is adjoined to the interior surface of a reaction vessel, at least one heat transfer media inlet header, and at least one heat transfer media outlet header; and the relief channel of each baffle is vented to the vessel exterior.
 31. The method of claim 17 wherein the at least one heat transfer baffle is fixably attached to the interior surface of the reaction vessel such that when the vessel contains contents in motion resulting in stress upon the at least one heat transfer baffles, the stress is attenuated.
 32. The method of claim 17 wherein the at least one heat transfer baffle is fixably attached to the interior surface of the reaction vessel at an angle relative to the interior wall or radius of the vessel, the angle being selected from the group consisting of about 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, 45°, 50°, 55°, 60°, 65°, 70°, 75°, 80°, 85°, and 90°.
 33. The method of claim 32 wherein the angle is about 60° relative to the interior wall or about 30° relative to the radius. 